Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

核磁共振法测定非离子表面活性剂 HLB 值的研究 2.几种混合体系 HLB 值的测定与计算

本文应用核磁共振法(NMR)测定了几种混合体系的 HLB 值与混合体系中各组分的 HLB 值。实验结果表明,混合体系中各组分在核磁共振图谱中的积分曲线高度也具有加和性。混合体系的 HLB 值是体系中各组分 HLB 值的加权平均值。因此,对混合体系的 HLB 值可以应用 NMR 法直接测定,也可应用 NMR 法测定各组分的 HLB值,通过计算求得,计算值与实测值完全一致。     

Treatment of severe diarrhoeal dehydration in hospital and home by oral fluids

This paper reports on 1330 infants, from birth to 24 months old, suffering from diarrhoea and moderate to severe dehydration who were hospitalized in Tehran University Hospital over a period of 11 months. Fifteen per cent of them had signs of shock and 36% had marasmus. All patients were treated orally in two phases: rehydration therapy and maintenance therapy. For rehydration, an isotonic fluid (sodium 80 mmol l-1, potassium 20 mmol l-1) was administered at a rate of 40 ml kg-1 h-1 until all signs of dehydration disappeared. Following complete hydration, the patients were discharged and maintenance therapy was performed at home, by mothers, administering Maintenance Solution (sodium 40 mmol l-1, potassium 30 mmol l-1) ad libitum. Intravenous fluids were not used, even in severe dehydration. The efficacy and safety of this regimen were confirmed by rapid and successful rehydration in 99.7% of the patients and correction of a wide variety of electrolyte abnormalities present on admission, though some relapsed. The study suggests that this protocol could be employed in varied types and severities of dehydration and electrolyte abnormalities, and could also be used in both well nourished infants and in those with severe marasmus. It also demonstrates that mothers can serve as effective health workers and can perform successful maintenance therapy. Nine per cent of treated children required readmission to hospital within 24 h of discharge and a further 8% were hospitalized elsewhere with recurrent symptoms.     

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.     

Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5-1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end-diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Synthesis and anti-tuberculous activity of diesters based on isosteviol and dicarboxylic acids

Diesters based on isosteviol and dicarboxylic acids were synthesized and tested for antituberculous activity. Isosteviol and some of its derivatives exhibit appreciable tuberculostatic properties in vitro, the activity being dependent on the length of the polymethylene spacer connecting two ent-beyeran fragments. The mechanism of the antituberculous action of isosteviol derivatives are discussed. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 9, pp. 12–13, September, 2006.